Phylogenomics of nontuberculous mycobacteria respiratory infections in people with cystic fibrosis.

Nontuberculous mycobacteria (NTM) can cause severe pulmonary disease in people with cystic fibrosis (pwCF). These infections present unique challenges for diagnosis and treatment, prompting a recent interest in understanding NTM transmission and pathogenesis during chronic infection. Major gaps remain in our knowledge regarding basic pathogenesis, immune evasion strategies, population dynamics, recombination potential, and the evolutionary implications of host and antibiotic pressures of long-term NTM infections in pwCF. Phylogenomic techniques have emerged as an important tool for tracking global patterns of transmission and are beginning to be used to ask fundamental biological questions about adaptation to the host during pathogenesis. In this review, we discuss the burden of NTM lung disease (NTM-LD), highlight the use of phylogenomics in NTM research, and address the clinical implications associated with these studies.

Combinatorial Pharmacogenomic Testing Improves Outcomes for Older Adults With Depression.

OBJECTIVE: Evaluate the clinical utility of combinatorial pharmacogenomic testing for informing medication selection among older adults who have experienced antidepressant medication failure for major depressive disorder (MDD). DESIGN: Post hoc analysis of data from a blinded, randomized controlled trial comparing two active treatment arms. SETTING: Psychiatry specialty and primary care clinics across 60 U.S. community and academic sites. PARTICIPANTS: Adults age 65 years or older at baseline (n = 206), diagnosed with MDD and inadequate response to at least one medication on the combinatorial pharmacogenomic test report during the current depressive episode. INTERVENTION: Combinatorial pharmacogenomic testing to inform medication selection (guided-care), compared with treatment as usual (TAU). OUTCOMES: Mean percent symptom improvement, response rate, and remission rateat week 8, measured using the 17-item Hamilton Depression Rating Scale; medication switching; and comorbidity moderator analysis. RESULTS: At week 8, symptom improvement was not significantly different for guided-care than for TAU (∆ = 8.1%, t = 1.64, df = 187; p = 0.102); however, guided-care showed significantly improved response (∆ = 13.6%, t = 2.16, df = 187; p = 0.032) and remission (∆ = 12.7%, t = 2.49, df = 189; p = 0.014) relative to TAU. By week 8, more than twice as many patients in guided-care than in TAU were on medications predicted to have no gene-drug interactions (χ2 = 19.3, df = 2; p <0.001). Outcomes in the guided-care arm showed consistent improvement through the end of the open-design 24-week trial, indicating durability of the effect. Differences in outcomes between arms were not significantly impacted by comorbidities. CONCLUSIONS: Combinatorial pharmacogenomic test-informed medication selection improved outcomes over TAU among older adults with depression.

Resensitization to Crizotinib by the Lorlatinib ALK Resistance Mutation L1198F.

In a patient who had metastatic anaplastic lymphoma kinase (ALK)-rearranged lung cancer, resistance to crizotinib developed because of a mutation in the ALK kinase domain. This mutation is predicted to result in a substitution of cysteine by tyrosine at amino acid residue 1156 (C1156Y). Her tumor did not respond to a second-generation ALK inhibitor, but it did respond to lorlatinib (PF-06463922), a third-generation inhibitor. When her tumor relapsed, sequencing of the resistant tumor revealed an ALK L1198F mutation in addition to the C1156Y mutation. The L1198F substitution confers resistance to lorlatinib through steric interference with drug binding. However, L1198F paradoxically enhances binding to crizotinib, negating the effect of C1156Y and resensitizing resistant cancers to crizotinib. The patient received crizotinib again, and her cancer-related symptoms and liver failure resolved. (Funded by Pfizer and others; ClinicalTrials.gov number, NCT01970865.).

Comparing sensitivity to change using the 6-item versus the 17-item Hamilton depression rating scale in the GUIDED randomized controlled trial.

BACKGROUND: Previous research suggests that the 17-item Hamilton Depression Rating Scale (HAM-D17) is less sensitive in detecting differences between active treatment and placebo for major depressive disorder (MDD) than is the HAM-D6 scale, which focuses on six core depression symptoms. Whether HAM-D6 shows greater sensitivity when comparing two active MDD treatment arms is unknown. METHODS: This post hoc analysis used data from the intent-to-treat (ITT) cohort (N = 1541) of the Genomics Used to Improve DEpression Decisions (GUIDED) trial, a rater- and patient-blinded randomized controlled trial. GUIDED compared combinatorial pharmacogenomics-guided care with treatment as usual (TAU) in patients with MDD. Percent of symptom improvement, response rate and remission rate from baseline to week 8 were evaluated using both scales. Analyses were performed for the full cohort and for the subset of patients who at baseline were taking medications predicted by the test to have moderate or significant gene-drug interactions. A Mokken scale analysis was conducted to compare the homogeneity of HAM-D17 with that of HAM-D6. RESULTS: At week 8, the guided-care arm demonstrated statistically significant benefit over TAU when the HAM-D6 (∆ = 4.4%, p = 0.023) was used as the continuous measure of symptom improvement, but not when using the HAM-D17 (∆ = 3.2%, p = 0.069). Response rates increased significantly for guided-care compared with TAU when evaluated using both HAM-D6 (∆ = 7.0%, p = 0.004) and HAM-D17 (∆ = 6.3%, p = 0.007). Remission rates also were significantly greater for guided-care versus TAU using both measures (HAM-D6 ∆ = 4.6%, p = 0.031; HAM-D17 ∆ = 5.5%, p = 0.005). Patients in the guided-care arm who at baseline were taking medications predicted to have gene-drug interactions showed further increased benefit over TAU at week 8 for symptom improvement (∆ = 7.3%, p = 0.004) response (∆ = 10.0%, p = 0.001) and remission (∆ = 7.9%, p = 0.005) using HAM-D6. All outcomes showed continued improvement through week 24. Mokken scale analysis demonstrated the homogeneity and unidimensionality of HAM-D6, but not of HAM-D17, across treatment arms. CONCLUSIONS: The HAM-D6 scale identified a statistically significant difference in symptom improvement between combinatorial pharmacogenomics-guided care and TAU, whereas the HAM-D17 did not. The demonstrated utility of pharmacogenomics-guided treatment over TAU as detected by the HAM-D6 highlights its value for future biomarker-guided trials comparing active treatment arms. TRIAL REGISTRATION: Clinicaltrials.gov: NCT02109939. Registered 10 April 2014.

Rociletinib in EGFR-mutated non-small-cell lung cancer.

BACKGROUND: Non-small-cell lung cancer (NSCLC) with a mutation in the gene encoding epidermal growth factor receptor (EGFR) is sensitive to approved EGFR inhibitors, but resistance develops, mediated by the T790M EGFR mutation in most cases. Rociletinib (CO-1686) is an EGFR inhibitor active in preclinical models of EGFR-mutated NSCLC with or without T790M. METHODS: In this phase 1-2 study, we administered rociletinib to patients with EGFR-mutated NSCLC who had disease progression during previous treatment with an existing EGFR inhibitor. In the expansion (phase 2) part of the study, patients with T790M-positive disease received rociletinib at a dose of 500 mg twice daily, 625 mg twice daily, or 750 mg twice daily. Key objectives were assessment of safety, side-effect profile, pharmacokinetics, and preliminary antitumor activity of rociletinib. Tumor biopsies to identify T790M were performed during screening. Treatment was administered in continuous 21-day cycles. RESULTS: A total of 130 patients were enrolled. The first 57 patients to be enrolled received the free-base form of rociletinib (150 mg once daily to 900 mg twice daily). The remaining patients received the hydrogen bromide salt (HBr) form (500 mg twice daily to 1000 mg twice daily). A maximum tolerated dose (the highest dose associated with a rate of dose-limiting toxic effects of less than 33%) was not identified. The only common dose-limiting adverse event was hyperglycemia. In an efficacy analysis that included patients who received free-base rociletinib at a dose of 900 mg twice daily or the HBr form at any dose, the objective response rate among the 46 patients with T790M-positive disease who could be evaluated was 59% (95% confidence interval [CI], 45 to 73), and the rate among the 17 patients with T790M-negative disease who could be evaluated was 29% (95% CI, 8 to 51). CONCLUSIONS: Rociletinib was active in patients with EGFR-mutated NSCLC associated with the T790M resistance mutation. (Funded by Clovis Oncology; ClinicalTrials.gov number, NCT01526928.).

Correction to: A predictive model for distinguishing radiation necrosis from tumour progression after gamma knife radiosurgery based on radiomic features from MR images.

The original version of this article, published on 24 November 2017, unfortunately contained a mistake.

A predictive model for distinguishing radiation necrosis from tumour progression after gamma knife radiosurgery based on radiomic features from MR images.

OBJECTIVES: To develop a model using radiomic features extracted from MR images to distinguish radiation necrosis from tumour progression in brain metastases after Gamma Knife radiosurgery. METHODS: We retrospectively identified 87 patients with pathologically confirmed necrosis (24 lesions) or progression (73 lesions) and calculated 285 radiomic features from four MR sequences (T1, T1 post-contrast, T2, and fluid-attenuated inversion recovery) obtained at two follow-up time points per lesion per patient. Reproducibility of each feature between the two time points was calculated within each group to identify a subset of features with distinct reproducible values between two groups. Changes in radiomic features from one time point to the next (delta radiomics) were used to build a model to classify necrosis and progression lesions. RESULTS: A combination of five radiomic features from both T1 post-contrast and T2 MR images were found to be useful in distinguishing necrosis from progression lesions. Delta radiomic features with a RUSBoost ensemble classifier had an overall predictive accuracy of 73.2% and an area under the curve value of 0.73 in leave-one-out cross-validation. CONCLUSIONS: Delta radiomic features extracted from MR images have potential for distinguishing radiation necrosis from tumour progression after radiosurgery for brain metastases. KEY POINTS: • Some radiomic features showed better reproducibility for progressive lesions than necrotic ones • Delta radiomic features can help to distinguish radiation necrosis from tumour progression • Delta radiomic features had better predictive value than did traditional radiomic features.

Clinical implications of a multiparametric magnetic resonance imaging based nomogram applied to prostate cancer active surveillance.

PURPOSE: Multiparametric magnetic resonance imaging may be beneficial in the search for rational ways to decrease prostate cancer intervention in patients on active surveillance. We applied a previously generated nomogram based on multiparametric magnetic resonance imaging to predict active surveillance eligibility based on repeat biopsy outcomes. MATERIALS AND METHODS: We reviewed the records of 85 patients who met active surveillance criteria at study entry based on initial biopsy and who then underwent 3.0 Tesla multiparametric magnetic resonance imaging with subsequent magnetic resonance imaging/ultrasound fusion guided prostate biopsy between 2007 and 2012. We assessed the accuracy of a previously published nomogram in patients on active surveillance before confirmatory biopsy. For each cutoff we determined the number of biopsies avoided (ie reliance on magnetic resonance imaging alone without rebiopsy) over the full range of nomogram cutoffs. RESULTS: We assessed the performance of the multiparametric magnetic resonance imaging active surveillance nomogram based on a decision to perform biopsy at various nomogram generated probabilities. Based on cutoff probabilities of 19% to 32% on the nomogram the number of patients who could be spared repeat biopsy was 27% to 68% of the active surveillance cohort. The sensitivity of the test in this interval was 97% to 71% and negative predictive value was 91% to 81%. CONCLUSIONS: Multiparametric magnetic resonance imaging based nomograms may reasonably decrease the number of repeat biopsies in patients on active surveillance by as much as 68%. Analysis over the full range of nomogram generated probabilities allows patient and caregiver preference based decision making on the risk assumed for the benefit of fewer repeat biopsies.

Patterns of care of radiation therapy in patients with stage IV rectal cancer: a Surveillance, Epidemiology, and End Results analysis of patients from 2004 to 2009.

BACKGROUND: According to the 2013 National Comprehensive Cancer Network guidelines, pelvic radiation therapy (RT) is one of the preferred regimens for patients with metastatic rectal cancer (mRC). The objective of this study was to analyze patterns of care and outcomes data for the receipt of RT among patients with mRC using the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: Patients with stage IV rectal or rectosigmoid cancer were identified in the SEER database (2004-2009). Patients were stratified according to their primary disease site (rectum vs rectosigmoid), tumor (T) classification, and lymph node (N) classification. Treatment regimens (with or without surgical resection, with or without RT) were recorded. The Fisher exact test was used to compare RT rates based on stratified factors. Two and five-year survival rates were compared among treatment groups. RESULTS: In total, 6873 patients with stage IV rectal cancer and 3417 patients with rectosigmoid cancer were identified. Overall, 20.5% of patients with rectal cancer underwent surgery alone, whereas 38.7% received RT with or without surgery. Within the rectosigmoid group, 51.4% of patients underwent surgery alone, and 15.1% received RT with or without surgery. The use of RT differed significantly between patients with in situ (Tis) through T2 tumors versus T3/T4 tumors (P < .001) and between those with N0 disease versus N1/N2 disease (P < .001). The 2-year and 5-year survival rates differed between treatment groups, with the highest survival rates observed among those who received combined surgery and RT. CONCLUSIONS: The primary treatments for patients with mRC include RT with or without surgery. RT is used more commonly in patients with primary rectal (vs rectosigmoid) tumors, N0 disease, or Tis-T2 tumors. Treatment with combination surgery and RT is associated with prolonged survival.

Tiam1-regulated osteopontin in senescent fibroblasts contributes to the migration and invasion of associated epithelial cells.

The tumor microenvironment undergoes changes concurrent with neoplastic progression. Cancer incidence increases with aging and is associated with tissue accumulation of senescent cells. Senescent fibroblasts are thought to contribute to tumor development in aging tissues. We have shown that fibroblasts deficient in the Rac exchange factor Tiam1 promote invasion and metastasis of associated epithelial tumor cells. Here, we use a three-dimensional culture model of cellular invasiveness to outline several steps underlying this effect. We find that stress-induced senescence induces decreased fibroblast Tiam1 protein levels and increased osteopontin levels, and that senescent fibroblast lysates induce Tiam1 protein degradation in a calcium- and calpain-dependent fashion. Changes in fibroblast Tiam1 protein levels induce converse changes in osteopontin mRNA and protein. Senescent fibroblasts induce increased invasion and migration in co-cultured mammary epithelial cells. These effects in epithelial cells are ameliorated by either increasing fibroblast Tiam1 or decreasing fibroblast osteopontin. Finally, in seeded cell migration assays we find that either senescent or Tiam1-deficient fibroblasts induce increased epithelial cell migration that is dependent on fibroblast secretion of osteopontin. These findings indicate that one mechanism by which senescent fibroblasts promote neoplastic progression in associated tumors is through degradation of fibroblast Tiam1 protein and the consequent increase in secretion of osteopontin by fibroblasts.

Current status of magnetic resonance imaging (MRI) and ultrasonography fusion software platforms for guidance of prostate biopsies.

Prostate MRI is currently the best diagnostic imaging method for detecting PCa. Magnetic resonance imaging (MRI)/ultrasonography (US) fusion allows the sensitivity and specificity of MRI to be combined with the real-time capabilities of transrectal ultrasonography (TRUS). Multiple approaches and techniques exist for MRI/US fusion and include direct 'in bore' MRI biopsies, cognitive fusion, and MRI/US fusion via software-based image coregistration platforms.

Changes observed in multiparametric prostate magnetic resonance imaging characteristics correlate with histopathological development of chronic granulomatous prostatitis after intravesical Bacillus Calmette-Guerin therapy.

Administration of Bacillus Calmette-Guerin (BCG) has been shown to cause granulomatous prostatitis, a rare inflammatory process that can be mistaken for prostate cancer. We present a case of a 78-year-old man on active surveillance for prostate cancer with a subsequent diagnosis of high-grade urothelial carcinoma. After intravesical BCG therapy, he developed chronic granulomatous prostatitis. We present serial magnetic resonance imaging and biopsy data demonstrating the time interval between BCG administration and the manifestation of chronic granulomatous prostatitis.

Accuracy of multiparametric magnetic resonance imaging in confirming eligibility for active surveillance for men with prostate cancer.

BACKGROUND: Active surveillance (AS) is an attempt to avoid overtreatment of clinically insignificant prostate cancer (PCa); however, patient selection remains controversial. Multiparametric prostate magnetic resonance imaging (MP-MRI) may help better select AS candidates. METHODS: We reviewed a cohort of men who underwent MP-MRI with MRI/Ultrasound fusion-guided prostate biopsy and selected potential AS patients at entry using Johns Hopkins criteria. MP-MRI findings were assessed, including number of lesions, dominant lesion diameter, total lesion volume, prostate volume, and lesion density (calculated as total lesion volume/prostate volume). Lesions were assigned a suspicion score for cancer by MRI. AS criteria were reapplied based on the confirmatory biopsy, and accuracy of MP-MRI in predicting AS candidacy was assessed. Logistic regression modeling and chi-square statistics were used to assess associations between MP-MRI interpretation and biopsy results. RESULTS: Eighty-five patients qualified for AS with a mean age of 60.2 years and mean prostate-specific antigen level of 4.8 ng/mL. Of these, 25 patients (29%) were reclassified as not meeting AS criteria based on confirmatory biopsy. Number of lesions, lesion density, and highest MRI lesion suspicion were significantly associated with confirmatory biopsy AS reclassification. These MRI-based factors were combined to create a nomogram that generates a probability for confirmed AS candidacy. CONCLUSION: As clinicians counsel patients with PCa, MP-MRI may contribute to the decision-making process when considering AS. Three MRI-based factors (number of lesions, lesion suspicion, and lesion density) were associated with confirmatory biopsy outcome and reclassification. A nomogram using these factors has promising predictive accuracy for which future validation is necessary. Cancer 2013;119:3359-66. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.

Utility of multiparametric magnetic resonance imaging suspicion levels for detecting prostate cancer.

PURPOSE: We determine the usefulness of multiparametric magnetic resonance imaging in detecting prostate cancer, with a specific focus on detecting higher grade prostate cancer. MATERIALS AND METHODS: Prospectively 583 patients who underwent multiparametric magnetic resonance imaging and subsequent prostate biopsy at a single institution were evaluated. On multiparametric magnetic resonance imaging, lesions were identified and scored as low, moderate or high suspicion for prostate cancer based on a validated scoring system. Magnetic resonance/ultrasound fusion guided biopsies of magnetic resonance imaging lesions in addition to systematic 12-core biopsies were performed. Correlations between the highest assigned multiparametric magnetic resonance imaging suspicion score and presence of cancer and biopsy Gleason score on the first fusion biopsy session were assessed using univariate and multivariate logistic regression models. Sensitivity, specificity, negative predictive value and positive predictive value were calculated and ROC curves were developed to assess the discriminative ability of multiparametric magnetic resonance imaging as a diagnostic tool for various biopsy Gleason score cohorts. RESULTS: Significant correlations were found between age, prostate specific antigen, prostate volume, and multiparametric magnetic resonance imaging suspicion score and the presence of prostate cancer (p<0.0001). On multivariate analyses controlling for age, prostate specific antigen and prostate volume, increasing multiparametric magnetic resonance imaging suspicion was an independent prognosticator of prostate cancer detection (OR 2.2, p<0.0001). Also, incremental increases in multiparametric magnetic resonance imaging suspicion score demonstrated stronger associations with cancer detection in patients with Gleason 7 or greater (OR 3.3, p<0.001) and Gleason 8 or greater (OR 4.2, p<0.0001) prostate cancer. Assessing multiparametric magnetic resonance imaging as a diagnostic tool for all prostate cancer, biopsy Gleason score 7 or greater, and biopsy Gleason score 8 or greater separately via ROC analyses demonstrated increasing accuracy of multiparametric magnetic resonance imaging for higher grade disease (AUC 0.64, 0.69, and 0.72, respectively). CONCLUSIONS: Multiparametric magnetic resonance imaging is a clinically useful modality to detect and characterize prostate cancer, particularly in men with higher grade disease.

Can magnetic resonance-ultrasound fusion biopsy improve cancer detection in enlarged prostates?

PURPOSE: Patients with an enlarged prostate and suspicion of prostate cancer pose a diagnostic dilemma. The prostate cancer detection rate of systematic 12-core transrectal ultrasound guided biopsy is between 30% and 40%. For prostates greater than 40 cc this decreases to 30% or less. Magnetic resonance-ultrasound fusion biopsy has shown superior prostate cancer detection rates. We defined the detection rate of magnetic resonance-ultrasound fusion biopsy in men with an enlarged prostate gland. MATERIALS AND METHODS: We retrospectively analyzed the records of patients who underwent multiparametric prostate magnetic resonance imaging followed by magnetic resonance-ultrasound fusion biopsy at our institution. Whole prostate volumes were calculated using magnetic resonance imaging reconstructions. Detection rates were analyzed with respect to age, prostate specific antigen and whole prostate volumes. Multivariable logistic regression was used to assess these parameters as independent predictors of prostate cancer detection. RESULTS: We analyzed 649 patients with a mean±SD age of 61.8±7.9 years and a median prostate specific antigen of 6.65 ng/ml (IQR 4.35-11.0). Mean whole prostate volume was 58.7±34.3 cc. The overall detection rate of the magnetic resonance-ultrasound fusion platform was 55%. For prostates less than 40 cc the detection rate was 71.1% compared to 57.5%, 46.9%, 46.9% 33.3%, 36.4% and 30.4% for glands 40 to 54.9, 55 to 69.9, 70 to 84.9, 85 to 99.9, 100 to 114.9 and 115 cc or greater, respectively (p<0.0001). Multivariable logistic regression showed a significant inverse association of magnetic resonance imaging volume with prostate cancer detection, controlling for age and prostate specific antigen. CONCLUSIONS: Transrectal ultrasound guided and fusion biopsy cancer detection rates decreased with increasing prostate volume. However, magnetic resonance-ultrasound fusion biopsy had a higher prostate cancer detection rate compared to that of transrectal ultrasound guided biopsy in the literature. Magnetic resonance-ultrasound fusion biopsy represents a promising solution for patients with suspicion of prostate cancer and an enlarged prostate.

Ensemble projections of wildfire activity and carbonaceous aerosol concentrations over the western United States in the mid-21st century.

We estimate future wildfire activity over the western United States during the mid-21st century (2046-2065), based on results from 15 climate models following the A1B scenario. We develop fire prediction models by regressing meteorological variables from the current and previous years together with fire indexes onto observed regional area burned. The regressions explain 0.25-0.60 of the variance in observed annual area burned during 1980-2004, depending on the ecoregion. We also parameterize daily area burned with temperature, precipitation, and relative humidity. This approach explains ~0.5 of the variance in observed area burned over forest ecoregions but shows no predictive capability in the semi-arid regions of Nevada and California. By applying the meteorological fields from 15 climate models to our fire prediction models, we quantify the robustness of our wildfire projections at mid-century. We calculate increases of 24-124% in area burned using regressions and 63-169% with the parameterization. Our projections are most robust in the southwestern desert, where all GCMs predict significant (p<0.05) meteorological changes. For forested ecoregions, more GCMs predict significant increases in future area burned with the parameterization than with the regressions, because the latter approach is sensitive to hydrological variables that show large inter-model variability in the climate projections. The parameterization predicts that the fire season lengthens by 23 days in the warmer and drier climate at mid-century. Using a chemical transport model, we find that wildfire emissions will increase summertime surface organic carbon aerosol over the western United States by 46-70% and black carbon by 20-27% at midcentury, relative to the present day. The pollution is most enhanced during extreme episodes: above the 84th percentile of concentrations, OC increases by ~90% and BC by ~50%, while visibility decreases from 130 km to 100 km in 32 Federal Class 1 areas in Rocky Mountains Forest.

MRI characterization of the dynamic effects of 5α-reductase inhibitors on prostate zonal volumes.

INTRODUCTION: Prior studies of volumetric effects of 5α-reductase inhibitors (5ARIs) on the prostate have used transrectal ultrasound which provides poor differentiation of prostatic zones. We utilized high-resolution prostate MRI to evaluate the true dynamic effects of 5ARI in men who underwent multiple MRIs. MATERIALS AND METHODS: A retrospective study of patients who underwent serial 3.0 Tesla prostate MRI from 2007 to 2012 and were treated with 5ARI were studied. Nineteen patients who had a baseline MRI prior to 5ARI initiation and subsequent MRI follow up were selected. A randomly selected group of 40 patients who had not received any form of therapy was selected as the control cohort. Total prostate volume (TPV), transition zone volume (TZV), and peripheral zone volume (PZV) were calculated using 3D reconstructions and prostate segmentation from T2-weighted MRI. Changes in volumes were correlated with the duration of treatment using linear regression analysis. RESULTS: Following over 2 years of treatment, 5ARI decreased TPV significantly (16.7%, p < 0.0001). There were similar decreases in TZV (7.5%, p < 0.001) and PZV (27.4%, p = 0.0002) from baseline. In the control group, TPV and TZV increased (p < 0.0001) while PZV remained stable. When adjusted for the natural growth of prostate zonal volume dynamics seen in the control cohort, approximately 60% of the reduction of the TPV from 5ARI resulted from changes in the TZV and 40% of the reduction from changes in the PZV. CONCLUSIONS: 3.0 Tesla MRI characterizations of the dynamic effects of 5ARI on prostate zonal volumes demonstrate significant decreases in TPV, TZV, and PZV. 5ARI blocks the natural growth of TZV as men age and decreases both TZV and PZV below their baselines. As imaging technology improves, prostate MRI allows for more accurate assessment of drug effects on dynamic prostate volumes.

Adapting to the Adaptive Radiation Workflow: Incorporating Video Sign Out for Improved Safety and Efficiency as Part of Magnetic Resonance Image Guided Adaptive Radiation.

 : Magnetic resonance image guided adaptive radiation therapy (MRgART) represents a significant improvement in our ability to deliver therapeutic radiation. However, for the process of MRgART to be carried out safely and efficiently, the covering radiation oncologist must be aware of all aspects of a patient's case, because they will be required to recontour and replan the patient before each treatment. In this report, we will demonstrate our initial experience with a video sign-out process to convey the detailed level of information required for the covering physician to treat patients safely and effectively with MRgART. We then describe our optimized video sign-out process to allow for other centers to adopt a similar approach.

Polystyrene-poly(ethylene oxide) diblock copolymer: the effect of polystyrene and spreading concentration at the air/water interface.

Polystyrene-block-poly(ethylene oxide) (PS-PEO) is an amphiphilic diblock copolymer that undergoes microphase separation when spread at the air/water interface, forming nanosized domains. In this study, we investigate the impact of PS by examining a series of PS-PEO samples containing constant PEO (~17,000 g·mol(-1)) and variable PS (from 3600 to 200,000 g·mol(-1)) through isothermal characterization and atomic force microscopy (AFM). The polymers separated into two categories: predominantly hydrophobic and predominantly hydrophilic with a weight percent of PEO of ~20% providing the boundary between the two. AFM results indicated that predominantly hydrophilic PS-PEO forms dots while more hydrophobic samples yield a mixture of dots and spaghetti with continent-like structures appearing at ~7% PEO or less. These structures reflect a blend of polymer spreading, entanglement, and vitrification as the solvent evaporates. Changing the spreading concentration provides insight into this process with higher concentrations representing earlier kinetic stages and lower concentrations demonstrating later ones. Comparison of isothermal results and AFM analysis shows how polymer behavior at the air/water interface correlates with the observed nanostructures. Understanding the impact of polymer composition and spreading concentration is significant in leading to greater control over the nanostructures obtained through PS-PEO self-assembly and their eventual application as polymer templates.

Challenges facing newly qualified community nurses: a qualitative study.

This article describes a qualitative study that set out first to explore the challenges facing recently qualified nurses working in community and intermediate healthcare settings, and their perceptions of role and professional identity, and then to propose effective support structures. Data were gathered using individual interviews which were recorded, transcribed and analysed through categorization using four key themes: transition work; new learning; support and supervision; professional identity and integration. It was concluded that transition can be challenging and stressful but, despite the level of independent working in the community, participants can be helped to develop resilience by a supportive environment in which their developmental needs are identified and met. Recommendations are made concerning the need for a more structured and planned approach to induction and preceptorship.